CovidPapers, Recovery, the Oxford Connexion

Recovery is the large British multi-arm, phase 3 trial evaluating 6 potential treatments for Covid 19. 

A trial, including 11,000 patients, conducted under close supervision by two Oxford University professors, Peter Horby and Martin Landray. We add the opportunity to interview Martin Landray on 5th June 2020 in an interview which resulted in a “checknews” by Liberation (a french information platform). We come back on this trial which turns out to be dubious combining all the elements of what could become the summer saga, with scientific distortions certainly more astute than the "Big Data" study published by the Lancet and retracted a few days later.

Simultaneously to the stoppage of the hydroxychloroquine arm in Recovery, we observed a manipulation of the public opinion.

 

The results show a lethal rate of 23% and 25% for the placebo and hydroxychloroquine (HCQ) groups. How can we explain these mortality rates compared to those observed in France at 18%?

In France, 18% of patients who were hospitalised with covid symptoms19 died. Rates by age group are 26.6% for 70 years and over and 8.5% for 40-69 years old.

How could one explain such a difference between the two groups? In order to understand we would need to see the data from the Recovery trial. The age of patients appears to be higher in Recovery. If there is a 25% lethality rate after 28 days, then 75% have made it.  The rate may not be better than the placebo, but it would be important to know whether the treatment has allowed some to avoid dying and especially others to die given the exaggerated dose of hydroxychloroquine administered (2400 mg on the first day and 800 mg/day after). Thus no conclusion may be drawn from the results of this arm since the dosage can be criticized in terms of level of toxicity, even opponents of HCQ treatment are in agreement!

Other pathologies (comorbidities) that will undoubtedly have had an impact on the lethality rate should also be checked, knowing that in the Recovery protocol, not all patients were tested, some were included in the trial only on medical assessment.

On this aspect, much remains to be analysed and already the conclusion of the HCQ arm seems more than questionable; we will come back to it.

Another aberration: the dosage on patients in poor shape

Regarding the dosage used in the HCQ arm, Professor Landray told us that they had used the one used for amoebic dysentery.  According to the doctors we consulted, this condition is    never treated with hydroxychloroquine, but by hydroxyquinoline (INTETRIX)! We have found publications that talk about hydroxyquinoline. We had already addressed this point in detail in our previous article.

Such confusion seems unreal to say the least!

Professor Horby tried to divert the attention by correcting his colleague's statement in Libération. Supposedly Martin Landray was not talking about amoebic dysentery, but about abscess of the liver; a complication of the first condition. This disease was previously treated with chloroquine. But Professor Landray did mention amoebic dysentery. If it was not for a professor in the medical world, it would be called incompetence.

Extract from Martin Landray's interview

Extract from Martin Landray's write-up reviewed and approved by him

Professor Horby mentioned in the Liberation article a 1995 OMS document that would have served as the basis for the trial. We are therefore in the presence of two distinct diseases mentioned by the Recovery team to justify the dosage. However, these two diseases are not treated with hydroxychloroquine, but with contemporary medicines.  When we look at the Recovery protocol, it says that the dosage is based on plasma concentration to cure malaria. Malaria is treated with chloroquine and again not or very little with hydroxychloroquine. Moreover, Recovery dosages cannot be based on chloroquine, as the pharmacokinetics of these two molecules are different. (see Vidal).

We know that the proportions of elderly people at risk were higher than in France (18%) and that in the Discovery program (French trial) the load dose is 800mg and then 400mg. The Recovery team reported that HCQ was not cardio-toxic, but we can question the toxicity of this cohort of patient. In addition to this, India has warned the OMS about the high doses used by the Recovery team (some 4 times more than in the Indian or French trial).  Blatant medical error justified by the possible confusion between diseases.

On dosage, an additional element that caught our attention is the difference between three documents: protocol, statistical analysis and presentation. In the presentation, hydroxychloroquine is the only molecule whose grammage has not been specified.  All others have one.  There is also confusion between the protocol and the analysis plan. These inaccuracies and error serve the authors when one takes a close look.

There are significant differences between HCQ dosages depending on the documents we are looking at. Indeed, in the document relating to the protocol  dated 15 May (V6)  the dosages are fully in line with those of the Declared Protocol Plan.

However, a brand new document dated June 9, the Statistical Analysis Plan, reveals  a completely different dosage from the original protocol plan 

Additionally, did patients in the HCQ arm die faster than the placebo group? It is very likely that the answer is yes, but the results will never be given in detail. Thus the number of deaths could be the cumulative number of deceased patients (by overdose of HCQ and by covid19)

The Remdesivir has been included in the Recovery test since 26 May by decision of the authorities (MHRA) and Recovery as of 27 May 2020. This was presented to investigators in a document dated June 2.  The program allows the addition of a drug to bring the best of science during the trial.  In the interview on 5 June 2020, Professor Landray told us:

Remdesivir was never included in the ReCoveRy trial.

Currently, the following drugs are being tested: Lopinavir-ritonavir, low-dose corticosteroids, hydroxychloroquine (which we have now stopped), azithromycin, convalescent plasma and Tocilizumab.

On the 2nd June 2020 document we looked at, there were 3 pages on Remdesivir, and Mr. Landray told us "this is the educational material we provide to investigators, and page 15 to 17 talks about Remdesivir, because we are monitoring all the changes on treatments around the world, so that's the current state of research or results on this drug."

Finally, Remdesivir is not included in the test because at the time of the test, it was not available in the UK.

All these statements are, of course, misleading. This is not the only omission.  So either Landray doesn't know his own protocol - but in the interview he did have time to pick up the list of drugs and talk about Remdesivir on several occasions - or this omission is made on purpose so that no questions are asked.

In addition, inclusion of a drug in the trial is subject to an MHRA approval procedure.  This was the case for the HCQ. The authorization was requested on March 23 and obtained on March 25, Landray tells us. The inclusion of Remdesivir in March was possible because it was also officially tested in the Chinese Phase 3 trial. We note that as of March 26, no study had shown proven Remdesivir benefits, even minimal.  In order to avoid evaluating remdesivir on the mortality rate, a new indicator was created: the improvement of hospitalisation time. This is the only indicator where the Remdesivir has shown "a glimmer of hope". In the publication it is stated that it is not statistically significant, but that there is a marginal tendency for improvement, almost non-existent (see publication in the Lancet of the Chinese study NCT04257656). All this without taking into account the severe side effects caused to a significant number of patients.

An pharmacist specialist told us:

"It is a common practice in these trail to create a composite indicator to allow the inclusion of a molecule."

There is always an indicator that will show this famous statistically significant effect (or not for that matter as in the case of the Remdesivir).

Hydroxychloroquine is disqualified despite its antiviral and anti-inflammatory properties on the basis of a recognised factual indicator such as mortality rate without even looking at its ability to reduce hospitalization time for the 75% survivors. But Remdesivir it is brought in through the small door on a “glimmer of hope”.

The conclusion of Professor Horby and Professor Landray to recommend the withdrawal of hydroxychloroquine is not justifiable considering the arguments developed and appears to be blatantly biased, accompanied by manipulation with intent to never compare the properties of the HCQ against the Remdesivir. There is something shocking and extremely serious about their ethics of medical practice.

Let's take a closer look at Professors Landray and Horby, two professors with academic degrees and responsibilities.

Who is Professor Peter Horby?

A professor at Oxford Nuffield College who has a university curriculum and industry-wide collaboration such as the Executive Director of ISARIC  (International Severe Acute Respiratory and Emerging Infection Consortium) who has received 4.5 million pounds of funding for vaccine research.

On June 8, this institute chaired by Prof. Horby released a comprehensive report  on Covid19 patients with more than 67130 records and endless patient details. More big data.  Surprisingly, professor Horby has the ability to publish comprehensive data on Covid19 and has not yet published any information on the details of the analysis in Recovery. An even more surprising fact is that, given his proximity to China, and his work done upstream why did he not alert the authorities sooner?

On January 24, 2020, Professor Horby and Professor Hayden published an article  on Covid19 in The Lancet. A second paper from Professor Horby and Professor Hayden is published on 24 January. Another  article in pre-publication on 20 February with Professor Hayden present who also participated in  remdesivir trials in April

And the 3rd  article on Remdesivir in which Professor Hayden was originally one of the signatories but is no longer there as of April 24 on version 2 of the article. A question that will be asked.

 

It seems to us that it would have been very helpful for tCheckNews to ask questions about Professor Horby's conflicts of interest rather than trying to validate what we said.

 

We have an analysis  of John Ward, a British journalist and historian who has been running a blog for several years. He revealed the opioid addiction problems of former British Prime Minister Gordon Brown.

ERGO, another research centre run by Prof Horby, has received 14 million pounds from Astra Zeneca and Zuckerberg, the founder of Facebook.

John Ward says:

"As a psychologist specialized in "focus groups" with forty years of experience, I was trained to understand respondents' body language. In my professional opinion, during Andrew Marr's interview on May 10, Professor Horby showed all the signs of classic discomfort of an interviewee hiding the full image from his audience."

In addition, Professor Horby states that Remdesivir showed no effect in a small study (a study in which he participated and in which Professor Landray was Controller),  and then refers to Professor Fauci's study in the USA that would have shown this improvement in the time spent in the hospital. As for the HCQ, he says that we must be careful, because there are no conclusive results. 

But he makes no reference to the various positive studies for HCQ and there were a few. Omission

Who is Martin Landray?

He is a professor of medicine and epidemiology and one of the chief investigators of the Recovery trial at the University of Oxford.  In addition, he has many positions:

He is Research Director, Health Data Research UK, Acting Director of the Big Data Institute, Leader of Big Data and Computing Innovation.  Head of Clinical Informatics and Big Data at the NIHR Oxford Biomedical Research Centre. He is a member of the Royal College of Physicians of London, of the Higher Education Academy, of the British Pharmacological Society and of the European Society of Cardiology.

In the exchange of good practices around the interview report, Professor Landray removed several elements. We told him that it was important to the reader and he did not object to that, so we are now publishing it.  He told us about Gilead spontaneously without anything being asked of him.

Another point that got us interested was the numerous positions he holds.  He is, among other things, Research Director, Health Data Research UK, Acting Director of the Big Data Institute, Leader of Big Data and Computing Innovation, And Director of The Clinical Informatics and Big Data at the NIHR Oxford Biomedical Research Centre.

The Funding for the Big Data Institute comes from the Li Ka-shing Foundation, a Chinese philanthropist, and from the Robertson Foundation, founder of the Hedge Fund Tiger, which was one of  Gilead's largest shareholders .

But that's not all, Professor Landray is also the controller of Professor Horby's study.

For all these reasons, we suspect, Professor Landray of intentional lies as well as Professor Horby of manipulation of CheckNews because of blatant conflicts of interest. Recovery is like all other Remdesivir trials handled in the underhand by Gilead which holds its patent and AstraZeneca which has just signed an agreement with France and Germany for 400 million doses of a vaccine that does not yet exist.  This is designed to prevent placing a low-cost hydroxychloroquine therapy in direct competition with Remdesivir.  The only trial that tests Remdesivir versus hydroxychloroquine is the French discovery test, which is still silent for reasons that will elude us all. This will be the subject of another article.

What about the regulator in all this?

All we had to do now was question the role of the MHRA, the supreme body supposed to guard the temple. This regulator asked Recovery to look at the effect of hydroxychloroquine, it also authorized the inclusion of Remdesivir in the trial without tangible evidence of its therapeutic activity.

Is there still an independent regulator? One could ask the question of who sits on the MHRA? Among Board members, Anne Toni Rodgers and Amanda Calvert declare conflicts of interest with AstraZeneca, which has just announced a proposed merger with Gilead. AstraZeneca has also just signed a contract with several other countries to sell 2 or 3 billion euros worth of vaccine doses to European countries.

Closing the loop ?

A regulatory body, with members declaring direct conflicts with AstraZeneca, asked to analyze Recovery's arm containing hydroxychloroquine.

Trial investigators with unreported conflicts of interest with Gilead, AstraZeneca and the Bill Gates Foundation that hide the truth about their research, that manipulate opinion on available information and demonstrate at minimum, their incompetence  by giving massive doses of hydroxychloroquine.

Remdesivir included through the small door in the trial without making any noise and that is not mentioned in an interview on 3 occasions.  Remember that Remdesivir costs nearly $1 a dose at manufacturing but would be charged a minimum of 200 euros for treatment in COVID 19. One has to be careful as the price of medicines is discussed on a case-by-case basis depending on the indication; the prices mentioned range from 200 euros the treatment to a few thousand euros,

that's at least twenty times more than the Pr. Raoult treatment, which would bring in a lot of money, much more than hydroxychloroquine.

Price:  The cost of producing the remdesivir  was estimated by a  study in the Journal of Virus Eradication  at less than $1 per day of treatment ($0.93). A controlled manufacturing cost, although it would be far from the cheapest of the treatments currently being tested. By comparison, hydroxychloroquine has a production cost more than ten times lower ($0.08). To reach the final price of the remdesivir, additional costs and costs associated with the development of the product would have to be added.

According to analyst Evaluate, clinical trials conducted on the remdesivir against Covid-19 are expected to cost the U.S. laboratory around $150 million.  

A planned merger to become the world's largest pharmaceutical company.

Is the crime almost perfect?